Expanding Horizons: HER2-Targeted Antibody–Drug Conjugates in Advanced Triple-Negative Breast Cancer

HER2-targeted antibody–drug conjugates (ADCs) are emerging as a promising therapeutic option in advanced triple-negative breast cancer (TNBC). Clinical evidence, including the DESTINY-Breast04 trial, demonstrates meaningful antitumor activity in TNBC patients with low HER2 expression, with notable improvements in response duration and patient-reported outcomes. These findings suggest that select TNBC tumors may harbor sufficient HER2 expression to allow effective ADC-mediated cytotoxicity. The observed activity likely reflects the combination of targeted HER2 binding and the potent payload delivered by ADCs, enabling tumor cell kill even in traditionally HER2-low disease. Clinically, these data support broader biomarker-driven treatment strategies and highlight the potential for HER2-directed ADCs to fill a significant therapeutic gap in advanced TNBC, offering patients both improved efficacy and quality-of-life benefits.